{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T05:14:38Z","timestamp":1789535678293,"version":"build-2803163510"},"reference-count":66,"publisher":"Wiley","license":[{"start":{"date-parts":[[2022,3,25]],"date-time":"2022-03-25T00:00:00Z","timestamp":1648166400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004881","name":"Instituto Mexicano del Seguro Social","doi-asserted-by":"publisher","award":["CTFIS\/10RD\/12\/2011"],"award-info":[{"award-number":["CTFIS\/10RD\/12\/2011"]}],"id":[{"id":"10.13039\/501100004881","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004881","name":"Instituto Mexicano del Seguro Social","doi-asserted-by":"publisher","award":["FIS\/IMSS\/PROT\/G15\/1454"],"award-info":[{"award-number":["FIS\/IMSS\/PROT\/G15\/1454"]}],"id":[{"id":"10.13039\/501100004881","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004881","name":"Instituto Mexicano del Seguro Social","doi-asserted-by":"publisher","award":["209881"],"award-info":[{"award-number":["209881"]}],"id":[{"id":"10.13039\/501100004881","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004881","name":"Instituto Mexicano del Seguro Social","doi-asserted-by":"publisher","award":["98220625"],"award-info":[{"award-number":["98220625"]}],"id":[{"id":"10.13039\/501100004881","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005343","name":"Fundaci\u00f3n IMSS","doi-asserted-by":"publisher","award":["CTFIS\/10RD\/12\/2011"],"award-info":[{"award-number":["CTFIS\/10RD\/12\/2011"]}],"id":[{"id":"10.13039\/501100005343","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005343","name":"Fundaci\u00f3n IMSS","doi-asserted-by":"publisher","award":["FIS\/IMSS\/PROT\/G15\/1454"],"award-info":[{"award-number":["FIS\/IMSS\/PROT\/G15\/1454"]}],"id":[{"id":"10.13039\/501100005343","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005343","name":"Fundaci\u00f3n IMSS","doi-asserted-by":"publisher","award":["209881"],"award-info":[{"award-number":["209881"]}],"id":[{"id":"10.13039\/501100005343","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005343","name":"Fundaci\u00f3n IMSS","doi-asserted-by":"publisher","award":["98220625"],"award-info":[{"award-number":["98220625"]}],"id":[{"id":"10.13039\/501100005343","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CONACYT","award":["CTFIS\/10RD\/12\/2011"],"award-info":[{"award-number":["CTFIS\/10RD\/12\/2011"]}]},{"name":"CONACYT","award":["FIS\/IMSS\/PROT\/G15\/1454"],"award-info":[{"award-number":["FIS\/IMSS\/PROT\/G15\/1454"]}]},{"name":"CONACYT","award":["209881"],"award-info":[{"award-number":["209881"]}]},{"name":"CONACYT","award":["98220625"],"award-info":[{"award-number":["98220625"]}]},{"DOI":"10.13039\/501100004881","name":"IMSS","doi-asserted-by":"crossref","award":["CTFIS\/10RD\/12\/2011"],"award-info":[{"award-number":["CTFIS\/10RD\/12\/2011"]}],"id":[{"id":"10.13039\/501100004881","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004881","name":"IMSS","doi-asserted-by":"crossref","award":["FIS\/IMSS\/PROT\/G15\/1454"],"award-info":[{"award-number":["FIS\/IMSS\/PROT\/G15\/1454"]}],"id":[{"id":"10.13039\/501100004881","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004881","name":"IMSS","doi-asserted-by":"crossref","award":["209881"],"award-info":[{"award-number":["209881"]}],"id":[{"id":"10.13039\/501100004881","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004881","name":"IMSS","doi-asserted-by":"crossref","award":["98220625"],"award-info":[{"award-number":["98220625"]}],"id":[{"id":"10.13039\/501100004881","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Immunology Research"],"published-print":{"date-parts":[[2022,3,25]]},"abstract":"<jats:p>It is acknowledged that antiviral immune response contributes to dengue immunopathogenesis. To identify immunological markers that distinguish dengue fever (DF) and dengue hemorrhagic fever (DHF), 113 patients with confirmed dengue infection were analyzed at 6 or 7 days after fever onset. Peripheral blood mononuclear cells (PBMC) were isolated, lymphocyte subsets and activation biomarkers were identified by flow cytometry, and differentiation of T helper (Th) lymphocytes was achieved by the relative expression analysis of T-bet (Th1), GATA-3 (Th2), ROR-\u03b3 (Th17), and FOXP-3 (T regulatory) transcription factors quantified by real-time PCR. CD8+, CD40L+, and CD45+ cells show higher numbers in DF compared to DHF patients, whereas CD4+, CD19+, and CD25+ cells show higher numbers in DHF than DF patients. High expression of GATA-3 accompanied by low expression of T-bet indicates predominance of Th2 response. In addition, higher expression of FOXP-3 and reduced functional cytotoxic T cells (CD8+perforin+) were observed in DHF patients. In further experiments, PBMC were stimulated ex vivo with dengue virus E, NS3, NS4, and NS5 peptides, and proliferating T cell subsets were determined. Lower proliferative responses to NS3 and NS4 peptides and reduced CD8+ cytotoxic T cells were observed in DHF patients. Our results suggest that immune response to dengue is dysregulated with predominance of CD4+ T cells, low activation of Th1 cells, and downregulation of the antiviral cytotoxic activity during severe dengue, likely induced by regulatory T cells.<\/jats:p>","DOI":"10.1155\/2022\/9967594","type":"journal-article","created":{"date-parts":[[2022,3,26]],"date-time":"2022-03-26T00:05:06Z","timestamp":1648253106000},"page":"1-13","source":"Crossref","is-referenced-by-count":5,"title":["Low Activation of CD8+ T Cells in response to Viral Peptides in Mexican Patients with Severe Dengue"],"prefix":"10.1155","volume":"2022","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6485-9223","authenticated-orcid":true,"given":"Tania","family":"Estrada-Jim\u00e9nez","sequence":"first","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica de Oriente, HGZ5, Instituto Mexicano del Seguro Social, Km 4.5 Carretera Atlixco-Metepec, CP 74360 Metepec, Puebla, Mexico"},{"name":"Facultad de Medicina, Decanato de Ciencias M\u00e9dicas, Universidad Popular Aut\u00f3noma del Estado de Puebla, 21 Sur 1103, Puebla, CP 72410 Puebla, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6490-1364","authenticated-orcid":true,"given":"Lilian","family":"Flores-Mendoza","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica de Oriente, HGZ5, Instituto Mexicano del Seguro Social, Km 4.5 Carretera Atlixco-Metepec, CP 74360 Metepec, Puebla, Mexico"},{"name":"Departamento de Ciencias Qu\u00edmico Biol\u00f3gicas y Agropecuarias, Divisi\u00f3n de Ciencias e Ingenier\u00eda, Universidad de Sonora, Unidad Regional Sur, C.P. 85880 Navojoa, Sonora, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1388-3178","authenticated-orcid":true,"given":"Laura","family":"\u00c1vila-Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Coordinaci\u00f3n Auxiliar de Investigaci\u00f3n en Salud, Morelos, Instituto Mexicano del Seguro Social, Boulevard Ju\u00e1rez No. 18, Col. Centro C.P., 62000 Cuernavaca, Morelos, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3777-2130","authenticated-orcid":true,"given":"Carlos Francisco","family":"V\u00e1zquez-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Coordinaci\u00f3n Auxiliar de Investigaci\u00f3n en Salud, Veracruz Sur, Instituto Mexicano del Seguro Social, Calle Poniente 7 # 1350, Col. Centro, C.P., 94300 Orizaba, Veracruz, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7112-1489","authenticated-orcid":true,"given":"Gilma Guadalupe","family":"S\u00e1nchez-Burgos","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica Yucat\u00e1n, Instituto Mexicano del Seguro Social, M\u00e9rida, Yucat\u00e1n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7884-1406","authenticated-orcid":true,"given":"Ver\u00f3nica","family":"Vallejo-Ruiz","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica de Oriente, HGZ5, Instituto Mexicano del Seguro Social, Km 4.5 Carretera Atlixco-Metepec, CP 74360 Metepec, Puebla, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9415-6011","authenticated-orcid":true,"given":"Julio","family":"Reyes-Leyva","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica de Oriente, HGZ5, Instituto Mexicano del Seguro Social, Km 4.5 Carretera Atlixco-Metepec, CP 74360 Metepec, Puebla, Mexico"},{"name":"Posgrado en Ciencias Qu\u00edmicas, Facultad de Ciencias Qu\u00edmicas, Benem\u00e9rita Universidad Aut\u00f3noma de Puebla, 18 Sur y Avenida San Claudio, Colonia San Manuel, 72570 Puebla, Puebla, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12060"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00035-09"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.3402\/iee.v3i0.19839"},{"key":"4","article-title":"Dengue and severe dengue","author":"World Health Organization"},{"key":"5","article-title":"Media center \u201cdengue in the Americas reaches highest number of cases recorded\u201d recovered from","author":"Pan American Health Organization"},{"issue":"2","key":"6","first-page":"122","article-title":"Dengue in Mexico: an analysis of two decades","volume":"150","author":"I. Torres-Galicia","year":"2014","journal-title":"Gaceta Medica"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1038\/s41426-018-0168-0"},{"key":"8","volume-title":"Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control: New Edition","author":"World Health Organization","year":"2009"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0123-x"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1038\/nri3916"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1038\/nri3014"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2014.11.001"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00093"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.5.3623-3629.1999"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.5.2817"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1038\/gene.2014.83"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.1016\/bs.apcsb.2016.10.002"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0801974"},{"key":"19","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaa0526"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1305227110"},{"key":"21","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir012"},{"key":"22","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2013.10.023"},{"key":"23","doi-asserted-by":"publisher","DOI":"10.1016\/j.trstmh.2007.06.019"},{"key":"24","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines7010011"},{"key":"25","doi-asserted-by":"publisher","DOI":"10.1038\/nm887"},{"key":"26","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/843469"},{"key":"27","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.6.3821"},{"key":"28","doi-asserted-by":"publisher","DOI":"10.1086\/526790"},{"key":"29","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1505956112"},{"key":"30","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1010867107"},{"key":"31","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02125"},{"key":"32","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.9.5665-5675.2005"},{"key":"33","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1997.8925"},{"key":"34","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.5.3999-4004.1998"},{"key":"35","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02675-12"},{"key":"36","doi-asserted-by":"publisher","DOI":"10.1002\/iid3.271"},{"key":"37","doi-asserted-by":"publisher","DOI":"10.2217\/fmb.13.171"},{"key":"38","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2010.07.014"},{"key":"39","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.70.5.3108-3117.1996"},{"issue":"3","key":"40","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.4049\/jimmunol.154.3.1287","article-title":"Dengue virus-specific, HLA-B35-restricted, human CD8+ cytotoxic T lymphocyte (CTL) clones. Recognition of NS3 amino acids 500 to 508 by CTL clones of two different serotype specificities","volume":"154","author":"P. G. Livingston","year":"1995","journal-title":"The Journal of Immunology"},{"key":"41","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01424-16"},{"key":"42","doi-asserted-by":"publisher","DOI":"10.1038\/srep00051"},{"key":"43","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3053"},{"key":"44","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20052165"},{"key":"45","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxr029"},{"key":"46","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-695X.2000.tb01474.x"},{"key":"47","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12199"},{"key":"48","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-695X.2007.00273.x"},{"issue":"1","key":"49","first-page":"63","article-title":"Shift from a Th1-type response to Th2-type in dengue haemorrhagic fever","volume":"76","author":"U. C. Chaturvedi","year":"1999","journal-title":"Current Science"},{"key":"50","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/5197592"},{"key":"51","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0003520"},{"key":"52","doi-asserted-by":"publisher","DOI":"10.1086\/506451"},{"key":"53","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01980"},{"key":"54","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0004497"},{"key":"55","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiy360"},{"key":"56","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0221-9"},{"key":"57","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1103782108"},{"key":"58","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2006.10.014"},{"key":"59","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201948420"},{"key":"60","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20061381"},{"key":"61","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0001505"},{"key":"62","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-012-9855-0"},{"key":"63","doi-asserted-by":"publisher","DOI":"10.3390\/v12121435"},{"key":"64","doi-asserted-by":"publisher","DOI":"10.1016\/j.femsim.2004.11.012"},{"key":"65","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2006.00420.x"},{"key":"66","doi-asserted-by":"publisher","DOI":"10.1038\/nm0804-801"}],"container-title":["Journal of Immunology Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/jir\/2022\/9967594.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/jir\/2022\/9967594.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/jir\/2022\/9967594.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T05:22:17Z","timestamp":1675056137000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.hindawi.com\/journals\/jir\/2022\/9967594\/"}},"subtitle":[],"editor":[{"given":"Luiz Felipe","family":"Domingues Passero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,3,25]]},"references-count":66,"alternative-id":["9967594","9967594"],"URL":"https:\/\/doi.org\/10.1155\/2022\/9967594","relation":{},"ISSN":["2314-7156","2314-8861"],"issn-type":[{"value":"2314-7156","type":"electronic"},{"value":"2314-8861","type":"print"}],"subject":[],"published":{"date-parts":[[2022,3,25]]}}}